SYNTHESIS OF LONG-CHAIN FATTY ACIDS IN MITOCHONDRIA

1. 1. NADH is much more effective than NADPH in promoting the incorporation of acetate into the long-chain acids of sonicated guinea-pig heart mitochondria, aged in order to remove endogenous nicotinamide nucleotides. In the presence of sufficient NADH, NADPH has no effect and NADP+ inhibits. 2. 2. Added Krebs-cycle intermediates stimulate the incorporation of acetate in intact mitochondria, but have no effect on the incorporation of acetyl-CoA in sonicated mitochondria, in the presence of sufficient NADH. 3. 3. Fractionation of rat-liver mitochondria with digitonin with the use of marker enzymes showed that the system responsible for fatty acid synthesis is bound to the inner membrane. 4. 4. In mitochondria treated with digitonin the incorporation of malonyl-CoA is about as rapid as that of acetyl-CoA. In some sub-mitochondrial fractions, however, acetyl-CoA is much the better substrate, indicating that it is unlikely that malonyl-CoA is an intermediate in the incorporation of acetate. The incorporation of malonyl-CoA is probably preceded by decarboxylation to acetyl-CoA. 5. 5. ATP is an absolute requirement for the incorporation of acetyl-CoA or malonyl-CoA by heart sub-mitochondrial preparations, indicating that de novo synthesis does not take place in these preparations. © 1969.